The ubiquitous 2-oxoacid dehydrogenases are a family of very large multienzyme
complexes consisting of multiple copies of at least three enzymes which
catalyze the oxidative decarboxylation of several different 2-oxoacids,
resulting in acyl-CoA products. Members of this family include pyruvate
dehydrogenase (PDH), 2-oxoglutarate dehydrogenase (OGDH) and branched-chain 2-oxoacid dehydrogenase (BCDH). The three enzymes assembling to form these
complexes are the decarboxylase E1 (called E1p, E1o and E1b in PDH, OGDH and
BCDH, respectively), dihydrolipoamide acetyl, succinyl and branched-chain
transferase E2 (E2p, E2o and E2b, respectively) and dihydrolipoamide
dehydrogenase E3. The E3 component is identical in all three complexes (PDH,
OGDH and BCDH) and catalyzes the same reaction. The structural core of all 2-oxoacid dehydrogenase complexes (ODHc) is formed of multiple copies of E2
subunits, with the E1 and E3 subunits bound on the periphery. The E2 component
of the ODHc’s of both bacteria and eukaryotes serves as the structural core of
these multienzyme complexes and is comprised of three types of domains.
Starting with the N-terminus, there are 1–3 tandem repeated lipoyl domains
(LD) (see <PDOC50968>), followed by a peripheral subunit-binding domain (PSBD)
responsible for binding E1/E3 chains. The third domain is the C-terminal
catalytic domain (CD). The individual domains are separated by long, flexible
linker regions allowing large movements of the lipoyl domain(s) to enable
active site coupling. The PSBD domain binds E1 or E3, but not both
simultaneously. The flexible linker allows the PSBD domain (associated with
either E1 or E3) to move quite freely with respect to the core formed E2
catalytic domains [1,2,3,4,5].
The ~35-residue PSBD domain has a compact structure consisting of two short,
parallel α-helices (H1 and H2) separated by a loop (L1), a single helical
turn, and a further, less well-ordered loop (L2) (see PDB:1BAL>). The compact
structure of the PSBD domain is stabilized mainly by hydrophobic interactions.
The interactions between the PSBD domain and E3 are all mediated by charged
side chains, forming an 'electrostatic zipper'. The residues of the PSBD
domain involved in the interactions are all provided by helix H1 of this
domain. Helix H2 of PSBD does not interact with E3, but may be involved in
binding E1 [1,2,4].
The profile we developed covers the entire PSBD domain.
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